Comparative dynamics of MAPK/ERK signalling components and immediate early genes in the hippocampus and amygdala following contextual fear conditioning and retrieval

Comparative dynamics of MAPK/ERK signalling components and immediate early genes in the hippocampus and amygdala following contextual fear conditioning and retrieval
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DOI:
10.1007/s00429-013-0505-y
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发表时间:
2014-01-01
影响因子:
3.1
通讯作者:
Jocelyne, Caboche
Jocelyne, Caboche
中科院分区:
医学3区
文献类型:
--
作者:
Antoine, Besnard;Serge, Laroche;Jocelyne, Caboche

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在过去的几年里,多项研究试图揭示记忆再巩固与巩固相比的分子特征。在本研究中,我们使用MAPK/ERK 1/2通路的免疫细胞化学检测,跟踪激活的海马和杏仁核中的神经元回路,在巩固和再巩固的上下文恐惧条件反射(CFC)的记忆。我们报告的选择性差异的幅度和时间动态的激活ERK 1/2信号在不同的子区域之间的后训练和后检索期间,除了在齿状回,激活的模式是相似的。然后,我们专注于这个大脑区域,以剖析下游ERK 1/2信号传导成分的模式,包括ser 10上MSK-1和组蛋白H3的磷酸化,沿着CFC训练和恢复后立即早期基因(IEG)Arc/Arg3.1,c-Fos和Zif 268/Egr 1的诱导。我们发现,完成核小体的反应,以及诱导的IEGs较短的再巩固期间相比,巩固。我们的研究结果揭示了CFC训练和检索后巩固和再巩固过程的细胞机制,并进一步扩展了记忆再巩固不是机械地重复巩固的概念。此外,我们提供的证据表明,以前建立的CFC记忆的强度的特点是不同的模式的ERK 1/2激活在不同的海马和杏仁核子域CFC记忆回忆。我们的研究结果强调巩固和再巩固过程之间的差异,有关的背景恐惧记忆。
Over the past few years multiple studies have attempted to uncover molecular signatures of memory reconsolidation when compared to consolidation. In the present study we used immunocytochemical detection of the MAPK/ERK1/2 pathway, to track activated neuronal circuits in the hippocampus and amygdala recruited during the consolidation and reconsolidation of a contextual fear conditioning (CFC) memory. We report selective differences in magnitude and temporal dynamics of activated ERK1/2 signalling in different subregions of these two structures between the post-training and post-retrieval periods, except in the dentate gyrus, where the patterns of activation were similar. We then focused on this brain area to dissect out the patterns of downstream ERK1/2 signalling components, including the phosphorylation of MSK-1 and histone H3 on ser10, along with the induction of the Immediate Early Genes (IEGs) Arc/Arg3.1, c-Fos and Zif268/Egr1 following CFC training and retrieval. We found that the completion of the nucleosomal response as well as the induction of IEGs shorter during the reconsolidation period as compared to consolidation. Our results shed new light on the cellular mechanisms underlying the consolidation and reconsolidation processes engaged following CFC training and retrieval and further extend the notion that memory reconsolidation is not mechanistically a repetition of consolidation. In addition, we provide evidence that the strength of a previously established CFC memory is characterized by distinct patterns of ERK1/2 activation in different hippocampal and amygdalar subfields upon CFC memory recall. Our results emphasize the differences between consolidation and reconsolidation processes in relation to contextual fear memories.